Systematic ajmaline challenge in patients with long QT 3 syndrome caused by the most common mutation: a multicentre study

Europace. 2017 Oct 1;19(10):1723-1729. doi: 10.1093/europace/euw214.


Aims: Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patients with LQT3 caused by the most common mutation, SCN5A-E1784K.

Methods and results: Consecutive families in tertiary referral centres diagnosed with LQT3 caused by SCN5A-E1784K were included in the study. Besides routine clinical work-up, ajmaline challenge was performed after informed consent. A total of 23 subjects (11 female, mean age 27 ± 14 years) from 4 unrelated families with a family history of sudden cardiac death and familial diagnosis of the SCN5A-E1784K mutation underwent ajmaline challenge and genetic testing. Sixteen subjects (9 female) were found to be heterozygous carriers of SCN5A-E1784K. Ajmaline challenge was positive in 12 out of the 16 (75%) mutation carriers, but negative in all non-carriers. Following ajmaline, a significant shortening of the rate-corrected JT (JTc) interval was observed in mutation carriers. The baseline JTc interval was significantly longer in mutation carriers with a positive ajmaline challenge compared with those with a negative one.

Conclusion: Overlap of LQT3 and BrS in patients carrying the most common mutation is high. Therefore, ajmaline challenge represents an important step to rule out potential BrS overlap in these patients before starting sodium channel blockers for the beneficial effect of QT shortening in LQT3.

Keywords: Ajmaline; Brugada syndrome; Long QT syndrome; Overlap syndrome; Sodium channel blocker challenge.

Publication types

  • Multicenter Study

MeSH terms

  • Action Potentials / drug effects
  • Adolescent
  • Adult
  • Ajmaline / administration & dosage*
  • Anti-Arrhythmia Agents / administration & dosage*
  • Brugada Syndrome / diagnosis
  • Brugada Syndrome / genetics
  • Brugada Syndrome / physiopathology
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Electrocardiography
  • Female
  • Genetic Predisposition to Disease
  • Germany
  • Heart Rate / drug effects
  • Humans
  • Long QT Syndrome / diagnosis*
  • Long QT Syndrome / drug therapy
  • Long QT Syndrome / genetics*
  • Long QT Syndrome / physiopathology
  • Male
  • Middle Aged
  • Mutation*
  • NAV1.5 Voltage-Gated Sodium Channel / drug effects*
  • NAV1.5 Voltage-Gated Sodium Channel / genetics*
  • Phenotype
  • Predictive Value of Tests
  • Tertiary Care Centers
  • Time Factors
  • Voltage-Gated Sodium Channel Blockers / administration & dosage*
  • Young Adult


  • Anti-Arrhythmia Agents
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Voltage-Gated Sodium Channel Blockers
  • Ajmaline

Supplementary concepts

  • Long Qt Syndrome 3